Preliminary evidence of relationship between genetic markers and oncology patient quality of life

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 7 de junio del 2004

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English

Presenter: J.A. Sloan
Presenter's Affiliation: The North Central Cancer Treatment Group
Type of Session: Plenary

Background

  • Genetic variation has been linked to a number of factors that affect quality of life (QOL) including depression, suicide, alcohol use, tobacco use, and psychiatric disorders
  • The effects of cancer treatment and outcomes have a profound effect on patients' QOL
  • It is possible that pre-treatment, baseline genetic markers are associated with QOL independent of treatment or outcome
  • This study was undertaken to identify possible pre-treatment genetic markers that may predict for QOL

Materials and Methods

  • Patients were enrolled in a randomized trial of stage IV colorectal cancer (CRC) comparing 3 different chemotherapy regimens were assessed for pre-treatment genetic markers
  • 22 genetic variants from 11 genes that are known to be associated with CRC and have a relationship to cellular metabolism were selected for investigation
  • Patients were excluded if they could not be assessed for QOL prior to treatment and from whom genetic sampling could not be performed
  • QOL was assessed using the Symptoms Distress Scale (SDS) (including subscales for fatigue, outlook, and total score) and the Uniscale Numeric Analog Scale
  • The study was designed to detect differences of 5 points on the QOL scales with a power of 90%

Results

  • 2/22 markers were excluded from analysis due to a lack of heterogeneity among patients (>95% of patients had similar expression of these genes)
  • 13/80 possible genetic relationships were significantly associated with QOL scores
  • The PPDY5 gene (associated with cellular metabolism) was significantly associated with fatigue with a 10.8 point difference on QOL scores between gene alleles (p=0.008): the A/A genotype was associated with increased fatigue
  • The TYMS TSER gene (associated with DNA synthesis) was found to be associated with lower overall SDS score, fatigue, and outlook (p=0.007, p=0.02, and p=0.007, respectively)
  • Covariate analysis for other factors that may affect QOL such as age, gender, performance status, and previous chemotherapy did not change association of the 13 genes to QOL scores

Author's Conclusions

  • Pretreatment genetic markers can predict for post-treatment QOL independent of treatment toxicity or treatment outcome
  • The study is limited in the small number of genes that were examined and broadening of the search for genetic markers may yield genetic markers with stronger associations to QOL
  • Identification of patients at high risk for decreased QOL based on genetic markers may lead to personalized therapy in the form of prophylactic administration of QOL interventions
  • A prospective study of genetic markers and QOL is warranted

Clinical/Scientific Implications

This study is the first to show that pre-treatment genetic markers may be independently associated with QOL.  QOL is often an overlooked aspect of cancer treatment and can severely affect a patient's perception of treatment outcome.  The identification of patients who are at high risk for impaired QOL would allow targeted aggressive treatment that may lead to improved overall QOL in the patient population.  As was stated by the authors, this study examined only a small number of targeted genes, and other genes that may have a stronger association with QOL may exist.  Identification of these genes would significantly improve our ability to predict for QOL.  While the results of this study are intriguing, the use of these genetic markers is not ready for widespread clinical utilization.  A prospective study which identifies patients at high risk for impaired QOL with randomization of targeted QOL therapy and close QOL follow-up is needed before this becomes clinically applicable.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.

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